Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
J Periodontal Res. 2012 Feb;47(1):55-61. doi: 10.1111/j.1600-0765.2011.01404.x. Epub 2011 Sep 6.
As epithelial cells function as a mechanical barrier, the permeability of the gingival epithelial cell layer indicates a defensive capability against invasion by periodontal pathogens. We have reported the expression of claudin-1 and E-cadherin, key regulators of permeability, in the gingival junctional epithelium. Irsogladine maleate (IM) is a medication for gastric ulcers and also regulates Aggregatibacter actinomycetemcomitans-stimuated chemokine secretion and E-cadherin expression in gingival epithelium. In this study, we have further investigated the effects of IM on the barrier functions of gingival epithelial cells under inflammatory conditions.
We examined the permeability, and the expression of claudin-1 and E-cadherin, in human gingival epithelial cells (HGECs) stimulated with tumor necrosis factor (TNF)-α, with or without IM.
TNF-α increased the permeability of HGECs, and IM abolished the increase. TNF-α reduced the expression of E-cadherin in HGECs, and IM reversed the reduction. In addition, immunofluorescence staining showed that TNF-α disrupted claudin-1 expression in HGECs, and IM reversed this effect.
The results suggest that IM reverses the TNF-α-induced disruption of the gingival epithelial barrier by regulating E-cadherin and claudin-1.
上皮细胞作为机械屏障，其功能是防止牙周致病菌的侵袭。我们曾报道过闭锁蛋白-1 和 E-钙黏蛋白在牙龈结合上皮中的表达，它们是调节通透性的关键调节因子。马来酸伊索拉定（IM）是一种治疗胃溃疡的药物，还可以调节牙龈上皮中 Aggregatibacter actinomycetemcomitans 刺激趋化因子的分泌和 E-钙黏蛋白的表达。在本研究中，我们进一步研究了 IM 在炎症条件下对牙龈上皮细胞屏障功能的影响。
我们检测了肿瘤坏死因子（TNF）-α刺激的人牙龈上皮细胞（HGEC）的通透性以及 claudin-1 和 E-钙黏蛋白的表达情况，同时还检测了有无 IM 的情况。
TNF-α增加了 HGEC 的通透性，而 IM 则消除了这种增加。TNF-α降低了 HGEC 中 E-钙黏蛋白的表达，而 IM 则逆转了这种降低。此外，免疫荧光染色显示 TNF-α破坏了 HGEC 中闭锁蛋白-1 的表达，而 IM 则逆转了这种效应。
这些结果表明，IM 通过调节 E-钙黏蛋白和闭锁蛋白-1来逆转 TNF-α 诱导的牙龈上皮屏障破坏。
